SUMMARY FOR BIOMARKERS/PATHOLOGY CORE The Biomarkers/Pathology Core will provide post-mortem diagnoses and biomarker analyses for patients and control subjects enrolled in the Clinical Core and for other well documented AD cases and controls. The approaches will be state-of-the-art and consistent with 21st century brain banking procedures, and will extend neuropathology core procedures to include targeted mass spectrometric assays to identify and quantitate AD- related biomarkers, as well as to establish induced pluripotent stem cells (iPSCs) from AD patients, innovative approaches which are essential to meet the increasingly sophisticated needs of the AD research community. Thus, the Biomarkers/Pathology Core will provide staff, technical resources, laboratory facilities and expertise for the three main Aims. Aim 1 will establish a Yale Neuropathology Core that will conduct postmortem examinations on Yale-ADRC patients and for other well documented AD cases and controls; and maintain a bank of unfixed frozen and fixed tissue from the ADRC control and patients with AD or other dementing neurodegenerative conditions. Aim 2 will establish and apply quantitative targeted mass spectrometric assays for the analysis of human AD brain samples and biofluids. This will include analysis of unfractionated and fractionated brain tissue, and CSF using MRM and SWATH mass spectrometry methods. Aim 3 will establish procedures for generation of Induced Pluripotent Stem Cells (iPSCs) from human AD patients. The Biomarkers/Pathology Core will closely interact with the other Cores of the Yale ADRC and provide tissue, methodologies and advice to Projects and Pilot Projects users in the ADRC, Yale researchers with an interest in AD, neurodegenerative disease and aging, and with other ADRCs. 1